It has been clearly demonstrated that limb immobilization affects muscle and the force that it can exert. This effect can have significant functional consequences. Although the precise control of muscle force is achieved by varying motor-unit activity, little is known about the influence of immobilization on motor-unit properties. In order to address this issue, the investigator proposes to examine the effects of immobilization on the properties and segmental interactions of motor neurons, motor units, and muscle receptors. The applicant's approach to this topic has two unique features: (1)the studies have been designed to use both an experimental animal paradigm and a conscious human paradigm so that behavior and invasive, mechanistic observations can be integrated; and (2) the studies will focus on the unexpected effects of immobilization since they represent some of the boundary conditions that determine various characteristics of the segmental motor system. In conscious human, the effects of immobilization on the contributions of motor unit recruitment and discharge rate to the gradation of muscle force will be examined (Aim 1) and on the fatigue related changes in discharge variability (Aim 2a). These effects will be quantified in terms of the upper limit of motor-unit recruitment, modulation of discharge rate (range, variability, and pattern), change in endurance time, and impairment of performance. Since afferent feedback has been implicated as a mechanism underlying the change in motor-unit discharge with fatigue, the applicants propose to determine the effect of an anesthetic block of small-diameter axons in humans (Aim 2b) and changes in the coupling between muscle receptors and motor units in anesthetized cats (Aim 2c) during fatiguing activity. Furthermore, because the remodeling of neuromuscular junctions may contribute to the absence of a decrease in fatigability with immobilization and in the appearance of "no-force" units, the applicants plan to measure neuromuscular propagation to determine the susceptibility of neuromuscular junctions to failure in both anesthetized cats and conscious humans (Aim 3). The observation of no-force units provides further evidence that immobilization affects muscle, perhaps even in the transmission of force from the active muscle fibers to the tendon. Selected mechanical effects on motor units in anesthetized cats will be quantified by measuring the nonlinear summation of the force exerted by pairs of motor units and the stiffness of homogeneous groups of motor units (Aim 4). Centrally, the effects of immobilization on motor neurons will be examined by measuring the post-synaptic response of neurons to feedback from muscle receptors and by measuring various intrinsic biophysical properties (Aim 5). It is anticipated that these studies will contribute new and useful information on fundamental issues related to the adaptive properties of the segmental motor system and on the functional consequences of limb immobilization, particularly after an orthopedic injury.